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Prevention of Cancer by Nutrition

The increased awareness of the protective role of dietary antioxidants is due largely to the results of epidemiological studies undertaken in the developing countries and in the USA. Researchers found that dietary levels of the major antioxidant vitamins could be related to the prevalence of cardiovascular diseases and cancer; in general the higher the intake of these vitamins the lower the level of disease.(1,2) Laboratory experiments demonstrated that dietary antioxidants could reduce the degree of oxidation of cholesterol that was associated with atherosclerosis and depress tumour growth by mechanisms still not fully understood but believed to act by preventing free radical damage to DNA or the production of carcinogenic metabolites from food or foreign chemicals. The next step was to initiate intervention studies in populations susceptible to cancer, studies in China supported by the US National Institutes of Health (NIH) showed that dietary supplementation with nutritional antioxidants could reduce the incidence of cancer in the 'at risk' populations.(3,4) Treatment of Cancer by Nutrition

While it is now widely accepted that nutritional factors can act to prevent some forms of cancer there is less recognition of the therapeutic potential of antioxidant therapy to arrest or cure diseases. The populist literature abounds with reports of miraculous cures of cancer, these have been either isolated cases of recovery or reported by doctors usually outside the mainstream of medicine and mostly done without adequate monitoring or ineffective controls. In some instances the maverick researchers have been treated less than justly by the medical establishment.

The Pioneers

Two examples of the many that could be quoted serve to illustrate this situation.

Linus Pauling, the double Nobel prize winner, teamed up with Ewen Cameron, an eminent Scottish surgeon to pursue observations made by Cameron in his unfashionable Vale of Leven Hospital, that large doses up to 10g/day of vitamin C as sodium ascorbate could improve the survival time of patients with terminal cancer.(5) The observations made in Scotland were replicated in the USA and Canada and justified initiating placebo controlled clinical trials. As there was no potential profit in selling vitamin C no pharmaceutical company could be persuaded to undertake such expensive studies but after pressure from doctors and patients the NIH agreed to sponsor a clinical trial of sodium ascorbate that they designed without reference to Cameron or Pauling. The results of this trial were essentially negative. Pauling protested that the doses of ascorbate that were used were too low; that the duration of the study was much shorter than they had recommended and that the patient selection process was defective but the results of this study virtually were widely publicised and effectively put an end to Pauling's claim that vitamin C had any value in cancer treatment.

In the 1950s Dr. Max Gerson promulgated a dietary treatment for cancer that included high doses of antioxidant vitamins and other nutrients and published his results of fifty well documented cases who benefited from his programme.(6) No controlled studies were done and the Gerson dietary therapy has been largely derided by the medical establishment, but Gerson's precepts are still widely practised with a level of benefit to patients that can not readily be dismissed as a placebo effect.

Unfortunately both Pauling and Gerson did not live to see that many of their observations have been vindicated by the results of the Chinese cancer intervention trials. Neither of these eminent researchers appeared to recognise that the vitamins they were studying were acting as antioxidants and free radical scavengers but they were close to the truth when they attributed the benefits of the treatments to stimulation of the immune system.

Antioxidant Therapy in Breast Cancer

Now that the antioxidants have been shown to prevent cancer, interest in their possible curative potential has been rekindled, particularly as nutritional antioxidants are generally devoid of the major toxic side effects of current anti-cancer drugs, whether emanating from the test tube of the synthetic chemist or the bio-reactor of the bio-technologist.

Karl Folkers and other investigators(7) have shown that the blood levels of the naturally occurring antioxidant Coenzyme Q10 ( CoQ10 ) or ubiquinone are lower in patients with a variety of cancers than in matched controls. CoQ10 has also been shown to stimulate the host defence system and to inhibit growth of chemically induced neoplasias.(8) The commercial availability of this biochemical has encouraged investigators to determine if this substance has any potential anti-cancer activity in man. Ethical constraints make it practically impossible to perform clinical trials in cancer patients when single agents alone are used and this is even more difficult when nutrients are to be investigated. Consequently in most clinical trials of potential new therapies in cancer the agent under investigation is given in addition to conventional anticancer therapy and placebo alone controls are rarely used.

In man the natural antioxidant defences against free radical damage work in an integrated manner and experimental and clinical studies suggest that the natural antioxidants work synergistically; for example vitamin C is used by the body to regenerate vitamin E that is destroyed in inhibiting lipid peroxidation. Thus in the major antioxidant intervention study in Linxian, China against oesophageal cancer, tablets containing vitamins A, B1, B2, B3, C and E together with zinc, selenium and molybdenum in various combinations were tested.

In studies in women with breast cancer Lockwood and his colleagues(9) have tested CoQ10 combined with other antioxidant nutrients and fatty acids as an adjunct to conventional radio- and chemotherapy. In the Chinese studies which were aimed at preventing the development of oesophageal cancer doses of antioxidants that were up to double the US RDAs were used. Lockwood argued that because of the compromised metabolic picture of patients with advanced breast cancer who were already receiving powerful immunosuppresant therapy, much higher doses of antioxidants should be used. This approach could be justified as any risk from nutrient toxicity would be minimal against a background of the cytotoxic effects of the powerful chemotherapeutic drugs that the patients were already receiving. As it was impractical to determine the dose levels of the antioxidants by conventional animal studies as would be done with a novel anti-cancer drug, the levels used in the study were estimated from the known safe limits of each constituent of therapeutic regimen to be tested.

Some natural oils, plants and animals high in long chain polyunsaturated fatty acids (PUFAs) have been shown to have anti-tumour activity under laboratory conditions. Evening primrose oil containing the (-6 PUFA (-linolenic acid (GLA) appeared in uncontrolled clinical trials to be effective against some forms of cancer.(10) Fish oils containing the (-3 PUFAs, EPA and DHA also may protect against other forms of cancer.(11)

Women Patients

Thirty two women with breast cancer all of whom were regarded as being at high risk were included in Lockwood's study, their ages ranged from 32-81 years at the start of the trail. The first patients were started on the treatment in 1992 and further patients have been added in the years since. All patients were treated according to routine procedures for managing breast cancer in use at the Copenhagen clinic, they were given a combination of surgery, chemotherapy, radiotherapy and in some cases tamoxifen according to clinical need.

They were given a comprehensive check every three months and a full clinical examination including mammography and radiology and X-ray examination where indicated. Blood samples were taken and full blood haematological and biochemical profiles were determined, in addition to conventional determinants these included CoQ10 and antioxidant blood levels. The levels of the tumour fighting t-lymphocytes and their subsets, the natural killer cells and helper and suppressor cells, were counted. Open biopsies of the tumour sites were taken for histopathological examination.

The Researchers

Knut Lockwood, a Danish cancer specialist from Copenhagen, noted the work of Karl Folkers and his colleagues from Texas on CoQ10 levels in cancer patients that was published in 1982.(12) He approached Folkers with a view to exploring the potential of CoQ10 in the treatment of his women patients with breast cancer. They recruited the help of Sven Moesgaard of the Danish firm Pharma Nord to develop a feasible dosage regiment for Lockwood's patients. A Japanese researcher Takashi Hanioka later joined the team to perform the laboratory determinations. They decided to use a multivalent, or blunderbuss approach, and combine CoQ10 , the antioxidant vitamins and minerals with borage oil containing higher levels of GLA than evening primrose oil, and a concentrated fish oil preparation.(13)

Treatments - The Strategy and Weapons

The nutritional supplements given to the women in this study were provided by one manufacturer as commercially available preparations providing a full spectrum of recognised antioxidant nutrients:(not listed here - see issue 8 for full listing).

In the light of experience and in order to boost the blood levels of CoQ10, the daily dose of Bio-Quinone Q10 was increased to from 90mg to 390mg after the first year. Because of compliance problems due to the number of capsules required, the daily dose of the fatty acid preparations was reduced as shown above. These dose levels are now being used in the ongoing study.

It should be emphasised that supplements from other manufacturers should not be regarded as equivalent to the above product as the bioavailability of the active ingredients and especially CoQ10 has been shown to vary widely with the form in which the nutrient is presented. In the above formulation the CoQ10 is dissolved in a vegetable oil in a gelatine capsule with a bioavailability that is double that from a typical tablet.

Results

After the first year the patients showed a significant increase in the mean blood level of CoQ10 from 0.82mg/l to 1.6mg/l, similar increases were found in the levels of the other major antioxidants which have been maintained ever since. The average total lymphocyte count and the total number of natural killer cells increased significantly but there was no change in the helper/suppresser cell ratio. There has been a general improvement in the clinical status of the patients. Actuarial data suggest that four of the patients with the level of disease present in these patients could have been expected to have died during the period of the trial14 but to date, mid 1995, none of the women entered into the trial have died. None of the patients have shown evidence of progression of distant metastatic spread. All patients have maintained their body weights, the use of pain killers has been reduced and their quality of life measures have improved. In six of the patients there is evidence of some degree of remission with either disappearance of the tumour or absence of any evidence of enlargement or metastatic spread. By 1993 two patients had shown complete regression of tumoursand since then three additional cases have been reported.(13) One of these three cases had metastases derived from intra-ductal carcinoma of the breast and these were found to have disappeared during continued therapy. In a further patient with metastatic spread to the liver with usually a poor prognosis the liver metastases also appear to have disappeared. Despite the high levels of nutrition supplements given and the state of health of the women there were no significant adverse side effects attributable to the treatment.

Study Progress

Lockwood's studies are continuing and new patients are being added to the group but the study is planned to last for a further two years before a full assessment can be made of the long term benefits of the treatment. However, the results are sufficiently encouraging that further studies using CoQ10 are being planned in additional centres in different countries.
The studies of Lockwood and Folkers offer hope to women diagnosed with breast cancer and might encourage women with this common form of cancer to pressurise their oncologists to add CoQ10 and other antioxidant nutritional supplements to their usual chemotherapy regimens. There is now firm evidence that this adjunctive approach may increase the effectiveness of treatment with no toxicological penalties.

References

1 Halliwell B & Gutteridge JMC. Free Radicals in Biology and Medicine. Oxford University Press. Oxford. 1989
2 Folkers K, Ellis J, Yang O et al. in Vitamins and Cancer Prevention. pp103-118, Wiley-Liss. N.Y. 1991
3 Blot W, Li J-Y, Taylor R et al. Nutrition intervention trials in Linxian, China: Supplementation with specific vitamin/mineral combination, cancer incidence and disease specific mortality in the general population. J. Nat. Cancer Inst. 85: 1483-98, 1993.
4 Li J-Y, Taylor R, Li B. et al. Nutrition intervention trials in Linxian, China: Multiple vitamin /mineral supplementation, cancer incidence and disease specific mortality among adults with esophageal dysplasia. J. Nat.Cancer Inst. 85: 1492-148, 1993.
5 Cameron E. & Pauling L. Cancer and Vitamin C. Linus Pauling Institute, Menlo Park, California. 1979.
6 Gerson M. A Cancer Therapy: Results of Fifty Cases. Totality Books, Del Mar. 1958.
7 Folkers K, Brown R, Judy WV and Morita M. Survival of cancer patients on therapy with coenzyme Q10. Biochem.Biophys.Res. Comm. 192: 241-251, 1993.
8 Folkers K. Critique of 30 years of research on haematopoietic and immunological activities of coenzyme Q10 and potentiality for therapy of AIDS and cancer. Med.Chem. Res. (in press) 1994.
9 Lockwood K, Moesgaard S, and Folkers K. Partial and complete remission of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem. Biophys. Res. Comm. 199: 1504-8 , 1994.
10 Van der Merwe C.F., Booyens J and Katzeff IE. Oral gammalinolenic acid in 21 patients with untreatable malignancy. An ongoing pilot open clinical trial. Brit.J.Clin. Practice 41: 907-915, 1987.
11 Nielsen N and Hansen J. Gastric and colorectal cancer in Greenland. Diagnostic basis and minimum incidence. Scand. J. Gastroent. 14: 697-703, 1979.
12 Folkers K, Shizukiushi S, Takemura K , et al. Increase in levels of IgG in serum of patients treated with coenzyme Q10. Res. Comm. Path. Pharm. 38: 335-338, 1982.
13 Lockwood K, Moesgaard S, Hanioka T and Folkers K. Apparent partial remission of breast cancer in patients supplemented with nutritional antoxidants, essential fatty acids and coenzyme Q10. Mol. Aspects Medicine. 15: Supp. s231-s240. 1994.
14 Dombernowsky P, Brincker H, Hansen M. et al. Adjuvant therapy of premenopausal and menopausal high risk breast cancer patients. Present status of the Danish Breast Cancer Cooperative Group Trials. 77-B & 88-B. Acta Oncol. 27: 691-7, 1988

Further Information:

Professionals requiring detailed reports and copies of the published papers covering Lockwood's work can be obtained on request from Pharma Nord (UK) Ltd. Spital Hall, Mitford, Morpeth. NE 61 3PN.